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. 1992 Mar;51(3):313–317. doi: 10.1136/ard.51.3.313

Localisation and characterisation of substance P binding to human synovial tissue in rheumatoid arthritis.

D A Walsh 1, P I Mapp 1, J Wharton 1, R A Rutherford 1, B L Kidd 1, P A Revell 1, D R Blake 1, J M Polak 1
PMCID: PMC1004650  PMID: 1374227

Abstract

The neuropeptide substance P is found in perivascular and free unmyelinated nerve fibres in human synovial tissue. Quantitative receptor autoradiography was used to show specific, high affinity (Kd = 0.75 (0.21), nmol/l (mean (standard error of the mean)), low capacity (Bmax = 27.8 (7.9) amol/mm2) binding sites for substance P Bolton Hunter-labelled with iodine-125 localised to vascular endothelial cells in human synovial tissue. The binding could be saturated, was reversible, and was dependent on the magnesium concentration. Unlabelled substance P and neurokinin A competitively inhibited specific binding with 50% inhibition at concentrations of 1.25 (0.21) and 175 (29) nmol/l respectively. Neurokinin B (mumol/l) and calcitonin gene related peptide (1 mumol/l) did not inhibit binding. These binding sites show characteristics of the neurokinin 1 tachykinin receptor subtype. This provides further evidence that substance P may play a part in the vascular control of human synovium and may influence inflammatory processes in joints.

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Selected References

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  1. DeBlasi A., O'Reilly K., Motulsky H. J. Calculating receptor number from binding experiments using same compound as radioligand and competitor. Trends Pharmacol Sci. 1989 Jun;10(6):227–229. doi: 10.1016/0165-6147(89)90266-6. [DOI] [PubMed] [Google Scholar]
  2. Devillier P., Weill B., Renoux M., Menkès C., Pradelles P. Elevated levels of tachykinin-like immunoreactivity in joint fluids from patients with rheumatic inflammatory diseases. N Engl J Med. 1986 May 15;314(20):1323–1323. doi: 10.1056/NEJM198605153142018. [DOI] [PubMed] [Google Scholar]
  3. Ferrell W. R., Russell N. J. Extravasation in the knee induced by antidromic stimulation of articular C fibre afferents of the anaesthetized cat. J Physiol. 1986 Oct;379:407–416. doi: 10.1113/jphysiol.1986.sp016260. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Furchgott R. F. Role of endothelium in responses of vascular smooth muscle. Circ Res. 1983 Nov;53(5):557–573. doi: 10.1161/01.res.53.5.557. [DOI] [PubMed] [Google Scholar]
  5. Glyn J. H., Sutherland I., Walker G. F., Young A. C. Low incidence of osteoarthrosis in hip and knee after anterior poliomyelitis: a late review. Br Med J. 1966 Sep 24;2(5516):739–742. doi: 10.1136/bmj.2.5516.739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Grönblad M., Konttinen Y. T., Korkala O., Liesi P., Hukkanen M., Polak J. M. Neuropeptides in synovium of patients with rheumatoid arthritis and osteoarthritis. J Rheumatol. 1988 Dec;15(12):1807–1810. [PubMed] [Google Scholar]
  7. Holzer P. Local effector functions of capsaicin-sensitive sensory nerve endings: involvement of tachykinins, calcitonin gene-related peptide and other neuropeptides. Neuroscience. 1988 Mar;24(3):739–768. doi: 10.1016/0306-4522(88)90064-4. [DOI] [PubMed] [Google Scholar]
  8. Kidd B. L., Mapp P. I., Gibson S. J., Polak J. M., O'Higgins F., Buckland-Wright J. C., Blake D. R. A neurogenic mechanism for symmetrical arthritis. Lancet. 1989 Nov 11;2(8672):1128–1130. doi: 10.1016/s0140-6736(89)91491-8. [DOI] [PubMed] [Google Scholar]
  9. Lam F. Y., Ferrell W. R. Inhibition of carrageenan induced inflammation in the rat knee joint by substance P antagonist. Ann Rheum Dis. 1989 Nov;48(11):928–932. doi: 10.1136/ard.48.11.928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lee C. M., Campbell N. J., Williams B. J., Iversen L. L. Multiple tachykinin binding sites in peripheral tissues and in brain. Eur J Pharmacol. 1986 Nov 4;130(3):209–217. doi: 10.1016/0014-2999(86)90270-0. [DOI] [PubMed] [Google Scholar]
  11. Levine J. D., Clark R., Devor M., Helms C., Moskowitz M. A., Basbaum A. I. Intraneuronal substance P contributes to the severity of experimental arthritis. Science. 1984 Nov 2;226(4674):547–549. doi: 10.1126/science.6208609. [DOI] [PubMed] [Google Scholar]
  12. Levine J. D., Collier D. H., Basbaum A. I., Moskowitz M. A., Helms C. A. Hypothesis: the nervous system may contribute to the pathophysiology of rheumatoid arthritis. J Rheumatol. 1985 Jun;12(3):406–411. [PubMed] [Google Scholar]
  13. Levine J. D., Dardick S. J., Roizen M. F., Helms C., Basbaum A. I. Contribution of sensory afferents and sympathetic efferents to joint injury in experimental arthritis. J Neurosci. 1986 Dec;6(12):3423–3429. doi: 10.1523/JNEUROSCI.06-12-03423.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lotz M., Carson D. A., Vaughan J. H. Substance P activation of rheumatoid synoviocytes: neural pathway in pathogenesis of arthritis. Science. 1987 Feb 20;235(4791):893–895. doi: 10.1126/science.2433770. [DOI] [PubMed] [Google Scholar]
  15. Mapp P. I., Kidd B. L., Gibson S. J., Terry J. M., Revell P. A., Ibrahim N. B., Blake D. R., Polak J. M. Substance P-, calcitonin gene-related peptide- and C-flanking peptide of neuropeptide Y-immunoreactive fibres are present in normal synovium but depleted in patients with rheumatoid arthritis. Neuroscience. 1990;37(1):143–153. doi: 10.1016/0306-4522(90)90199-e. [DOI] [PubMed] [Google Scholar]
  16. Marceau F., Tremblay B., Couture R., Regoli D. Prostacyclin release induced by neurokinins in cultured human endothelial cells. Can J Physiol Pharmacol. 1989 Feb;67(2):159–162. doi: 10.1139/y89-026. [DOI] [PubMed] [Google Scholar]
  17. Marshall K. W., Chiu B., Inman R. D. Substance P and arthritis: analysis of plasma and synovial fluid levels. Arthritis Rheum. 1990 Jan;33(1):87–90. doi: 10.1002/art.1780330111. [DOI] [PubMed] [Google Scholar]
  18. Pernow B. Substance P. Pharmacol Rev. 1983 Jun;35(2):85–141. [PubMed] [Google Scholar]
  19. Rees D. D., Palmer R. M., Hodson H. F., Moncada S. A specific inhibitor of nitric oxide formation from L-arginine attenuates endothelium-dependent relaxation. Br J Pharmacol. 1989 Feb;96(2):418–424. doi: 10.1111/j.1476-5381.1989.tb11833.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Slowman-Kovacs S. D., Braunstein E. M., Brandt K. D. Rapidly progressive Charcot arthropathy following minor joint trauma in patients with diabetic neuropathy. Arthritis Rheum. 1990 Mar;33(3):412–417. doi: 10.1002/art.1780330316. [DOI] [PubMed] [Google Scholar]
  21. Smith J. A., Lang D. Release of endothelium-derived relaxing factor from pig cultured aortic endothelial cells, as assessed by changes in endothelial cell cyclic GMP content, is inhibited by a phorbol ester. Br J Pharmacol. 1990 Mar;99(3):565–571. doi: 10.1111/j.1476-5381.1990.tb12969.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Stanisz A., Scicchitano R., Stead R., Matsuda H., Tomioka M., Denburg J., Bienenstock J. Neuropeptides and immunity. Am Rev Respir Dis. 1987 Dec;136(6 Pt 2):S48–S51. doi: 10.1164/ajrccm/136.6_Pt_2.S48. [DOI] [PubMed] [Google Scholar]
  23. THOMPSON M., BYWATERS E. G. Unilateral rheumatoid arthritis following hemiplegia. Ann Rheum Dis. 1962 Dec;21:370–377. doi: 10.1136/ard.21.4.370. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Yaksh T. L. Substance P release from knee joint afferent terminals: modulation by opioids. Brain Res. 1988 Aug 23;458(2):319–324. doi: 10.1016/0006-8993(88)90474-x. [DOI] [PubMed] [Google Scholar]
  25. Yokota Y., Sasai Y., Tanaka K., Fujiwara T., Tsuchida K., Shigemoto R., Kakizuka A., Ohkubo H., Nakanishi S. Molecular characterization of a functional cDNA for rat substance P receptor. J Biol Chem. 1989 Oct 25;264(30):17649–17652. [PubMed] [Google Scholar]

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